NDUFA4
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
NDUFA4, mitochondrial complex associated is a protein that in humans is encoded by the NDUFA4 gene.[4] The NDUFA4 protein was first described to be a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[5] However, recent research has described NDUFA4 as a subunit of cytochrome c oxidase.[6] Mutations in the NDUFA4 gene are associated with Leigh's syndrome.[4]
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| Aliases | NDUFA4, CI-9k, CI-MLRQ, MLRQ, mitochondrial complex associated, COXFA4, NDUFA4 mitochondrial complex associated, MC4DN21, MRCAF1, MISTR1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603833; MGI: 107686; HomoloGene: 37629; GeneCards: NDUFA4; OMA:NDUFA4 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
The NDUFA4 gene is located on the p arm of chromosome 7 at position 21.3 with a total length of 8,234 base pairs.[4] The NDUFA4 gene produces a 9.4 kDa protein composed of 81 amino acids.[7][8]
NDUFA4 has traditionally been defined as a subunit of the enzyme NADH dehydrogenase (ubiquinone) (Complex I), the largest of the respiratory complexes.
More recent research has demonstrated that no perturbation of Complex I occurs upon NDUFA4 deletion, calling into question its role in this complex. It has been demonstrated that NDUFA4 plays a role in Complex IV function and biogenesis, however, with some authors suggesting that the NDUFA4 gene be renamed and the structure of both Complex I and Complex IV be re-evaluated.[6]
Clinical significance
Mutations in the NDUFA4 gene can result in Leigh's syndrome, a severe neurological disorder that typically arises in the first year of life. Disruption of Complex IV, also called cytochrome c oxidase or COX, is the most common cause of Leigh syndrome. Given that NDUFA4 has only recently been identified as a subunit of Complex IV rather than Complex I, patients with previously unexplained COX deficiencies could be genetically tested for NDUFA4 mutations.[4][9][10]
Interactions
NDUFA4 has many protein-protein interactions, including ubiquitin proteins such as ubiquitin C and UBL4A, as well as CUL3 and PARK7.[4]